Attacking pain at its source: new perspectives on opioids

@article{Stein2003AttackingPA,
  title={Attacking pain at its source: new perspectives on opioids},
  author={Christoph Stein and Michael Schäfer and Halina Machelska},
  journal={Nature Medicine},
  year={2003},
  volume={9},
  pages={1003-1008}
}
The treatment of severe pain with opioids has thus far been limited by their unwanted central side effects. Recent research promises new approaches, including opioid analgesics acting outside the central nervous system, targeting of opioid peptide–containing immune cells to peripheral damaged tissue, and gene transfer to enhance opioid production at sites of injury. 
Opioids and the skin: "itchy" perspectives beyond analgesia and abuse.
TLDR
Results clearly indicate that opioids play a specific role in skin homeostasis by modulating keratinocyte differentiation, wound healing, and inflammatory responses.
38 : Opioids
TLDR
Although the therapeutic and toxic doses are difficult to predict because of the development of tolerance with chronic use, the primary adverse event from excessive dosing is respiratory depression.
Targeting pain and inflammation by peripherally acting opioids
  • C. Stein
  • Biology, Medicine
    Front. Pharmacol.
  • 2013
TLDR
Future aims in drug development include the design of peripherally restricted opioid agonists, selective targeting of opioids to sites of painful injury and the augmentation of peripheral ligand and receptor synthesis, e.g., by gene therapy.
Opioids in rheumatic diseases
TLDR
The role of opioids in chronic rheumatic diseases is focused on and the peripheral effects of opioids on pain and inflammation in rhematic diseases will be outlined.
Opioids for the treatment of arthritis pain
TLDR
The role of conventional opioids in chronic arthritis is discussed and future developments and strategies exploiting peripheral effects of opioids on pain and inflammation will be outlined.
Peripherally applied opioids for postoperative pain: evidence of an analgesic effect? A systematic review and meta‐analysis
TLDR
This systematic review to evaluate the analgesic effect of peripherally applied opioids for acute postoperative pain found opioids applied peripherally at the site of surgery may produce postoperative analgesia with few side effects.
Peripheral opioid analgesia: Clinical applications
TLDR
In insight into the recent experience with the clinical applications of peripheral opioid analgesia, studies evaluating inflammatory pain conditions show clear evidence and the number and the sites of applications are increasing.
Opioids, sensory systems and chronic pain.
  • C. Stein
  • Medicine, Psychology
    European journal of pharmacology
  • 2013
Inhibiting the breakdown of endogenous opioids and cannabinoids to alleviate pain
TLDR
The effects of Dual enkephalinase inhibitors and FAAH inhibitors are compared and the progress in their rational design is described, to consider the challenges in their clinical development and opportunities for combination therapies.
Effect of transdermal opioids in experimentally induced superficial, deep and hyperalgesic pain
TLDR
This work has compared the analgesic and anti‐hyperalgesic effects of buprenorphine and fentanyl.
...
...

References

SHOWING 1-10 OF 116 REFERENCES
Immune Mechanisms in Pain Control
TLDR
Targeting of immune cells containing opioids to injured tissues is a novel concept of pain control and opens potential new therapeutic approaches.
Peripheral antinociceptive effects of morphine after burn injury
TLDR
Results confirm experimental data demonstrating a peripheral antinociceptive effects of opioids in inflamed tissue and heat–pain thresholds and pressure-pain thresholds were significantly increased by local morphine administration.
Analgesic effects of peripherally administered opioids in clinical models of acute and chronic inflammation
TLDR
Data indicate that peripheral opioid analgesia can be evoked in a model of chronic, but not acute, inflammatory pain, suggesting a temporal dependent mechanism needed for the expression of peripheral opiate analgesia during inflammation in humans.
New paths to pain relief
A better understanding of the mechanisms by which pain signals are relayed in the nervous system is paving the way for novel treatments.
No tolerance to peripheral morphine analgesia in presence of opioid expression in inflamed synovia.
TLDR
It is found that, despite an abundance of opioid-containing cells in pronounced synovitis, morphine is at least as effective as in patients without such cellular infiltrations, and there is no major downregulation of peripheral opioid receptors.
Intra‐articular morphine for pain relief after knee arthroscopy
TLDR
The aim of the present study was to evaluate the analgesic effects of intra‐articular morphine after knee arthroscopy and found that morphine administered through the EMT route is more effective than either orally or through the infusion route.
...
...